Ovr110 antibody compositions and methods of use

Abstract

The invention provides isolated anti-ovarian, pancreatic, lung or breast cancer antigen (Ovr110) antibodies that internalize upon binding to Ovr110 on a mammalian in vivo. The invention also encompasses compositions comprising an anti-Ovr110 antibody and a carrier. These compositions can be provided in an article of manufacture or a kit. Another aspect of the invention is an isolated nucleic acid encoding an anti-Ovr110 antibody, as well as an expression vector comprising the isolated nucleic acid. Also provided are cells that produce the anti-Ovr110 antibodies. The invention encompasses a method of producing the anti-Ovr110 antibodies. Other aspects of the invention are a method of killing an Ovr110-expressing cancer cell, comprising contacting the cancer cell with an anti-Ovr110 antibody and a method of alleviating or treating an Ovr110-expressing cancer in a mammal, comprising administering a therapeutically effective amount of the anti-Ovr110 antibody to the mammal.

1. An isolated antibody that binds to Ovr110 with a binding affinity of 10 −9  to 10 −13  M, wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by a hybridoma selected from the group consisting of American Type Culture Collection accession number PTA-5180, PTA-5855, PTA-5856 and PTA-5884. 
     
     
       2. The antibody of  claim 1 , wherein said antibody internalizes upon binding to Ovr110 on a mammalian cell. 
     
     
       3. The antibody of  claim 1  which is a monoclonal, chimeric, human or a humanized antibody. 
     
     
       4. The antibody of  claim 1 , wherein said antibody is a monoclonal antibody produced by a hybridoma selected from the group consisting of American Type Culture Collection accession number PTA-5180, PTA-5855, PTA-5856 and PTA-5884. 
     
     
       5. The antibody of  claim 1  which is conjugated to a growth inhibitory agent or a cytotoxic agent. 
     
     
       6. The antibody of  claim 5  wherein the cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 
     
     
       7. The antibody of  claim 6 , wherein the cytotoxic agent is a toxin selected from the group consisting of ricin, saponin, maytansinoid and calicheamicin. 
     
     
       8. The antibody of  claim 1 , wherein said antibody inhibits the growth of Ovr110-expressing cancer cells. 
     
     
       9. The antibody of  claim 1  which is a monoclonal, chimeric, humanized or human antibody. 
     
     
       10. The antibody of  claim 9  which is produced in bacteria. 
     
     
       11. The antibody of  claim 8 , wherein the cancer cells are from a cancer selected from the group consisting of ovarian, pancreatic, lung and breast cancer. 
     
     
       12. An isolated cell that produces the antibody of  claim 1 . 
     
     
       13. A composition comprising the antibody of  claim 1  and a carrier. 
     
     
       14. The composition of  claim 13 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
       15. The composition of  claim 13 , wherein the antibody is a monoclonal, chimeric, human or humanized antibody and the carrier is a pharmaceutical carrier. 
     
     
       16. A method of killing an Ovr110-expressing cancer cell, comprising contacting the cancer cell with the antibody of  claim 1 , thereby killing the cancer cell. 
     
     
       17. The method of  claim 16 , wherein the cancer cell is selected from the group consisting of ovarian, pancreatic, lung and breast cancer cell. 
     
     
       18. The method of  claim 16 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
       19. The method of  claim 18 , wherein the cytotoxic agent is a toxin selected from the group consisting of maytansinoid, ricin, saporin and calicheamicin or a radioisotope. 
     
     
       20. The method of  claim 16 , wherein the antibody is administered in conjunction with at least one chemotherapeutic agent. 
     
     
       21. The method of  claim 20  wherein the chemotherapeutic agent is paclitaxel or derivatives thereof. 
     
     
       22. A method for determining if cells in a sample express Ovr110 comprising
 (a) contacting a sample of cells with an Ovr110 antibody of  claim 1  under conditions suitable for specific binding of the Ovr110 antibody to Ovr110, and 
 (b) determining the level of binding of the antibody to cells in the sample, or the level of Ovr110 antibody internalization by cells in said sample, 
 wherein Ovr110 antibody binding to cells in the sample or internalization of the Ovr110 antibody by cells in the sample indicate cells in the sample express Ovr110. 
 
     
     
       23. A method for detecting Ovr110 overexpression in a subject in need thereof comprising,
 (a) combining a serum sample of a subject with an Ovr110 antibody of  claim 1  under conditions suitable for specific binding of the Ovr110 antibody to Ovr110 in said serum sample, 
 (b) determining the level of Ovr110 in the serum sample, and 
 (c) comparing the level of Ovr110 determined in step b to the level of Ovr110 in a control, 
 wherein an increase in the level of Ovr110 in the serum sample from the subject as compared to the control is indicative of Ovr110 overexpression in the subject. 
 
     
     
       24. The method of  claim 23  wherein the subject has cancer. 
     
     
       25. The method of  claim 24  wherein the subject has breast or ovarian cancer. 
     
     
       26. The antibody of  claim 1  which is detectably labeled. 
     
     
       27. The antibody of  claim 26  wherein the label is selected from the group comprising radiolabels, fluorescent labels, gold particles, and enzymatic labels. 
     
     
       28. An isolated antibody that competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by a hybridoma selected from the group consisting of American Type Culture Collection accession number PTA-5180, PTA-5855, PTA-5856 and PTA-5884. 
     
     
       29. The antibody of  claim 28  which is a monoclonal antibody produced by a hybridoma selected from the group consisting of American Type Culture Collection accession number PTA-5180, PTA-5855, PTA-5856 and PTA-5884. 
     
     
       30. The antibody of  claim 28  which is conjugated to a growth inhibitory agent or a cytotoxic agent. 
     
     
       31. The antibody of  claim 30  wherein the cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 
     
     
       32. The antibody of  claim 31 , wherein the cytotoxic agent is a toxin selected from the group consisting of ricin, saponin, maytansinoid and calicheamicin. 
     
     
       33. The antibody of  claim 28  which is detectably labeled. 
     
     
       34. The antibody of  claim 33  wherein the label is selected from the group comprising radiolabels, fluorescent labels, gold particles, and enzymatic labels. 
     
     
       35. An isolated cell that produces the antibody of  claim 28 . 
     
     
       36. A composition comprising the antibody of  claim 28  and a carrier. 
     
     
       37. The composition of  claim 36 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
       38. The composition of  claim 36 , wherein the antibody is a chimeric, human or humanized antibody and the carrier is a pharmaceutical carrier. 
     
     
       39. The antibody of  claim 1  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5180. 
     
     
       40. The antibody of  claim 1  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5855. 
     
     
       41. The antibody of  claim 1  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5856. 
     
     
       42. The antibody of  claim 1  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5884. 
     
     
       43. The antibody of  claim 1 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5180. 
     
     
       44. The antibody of  claim 1 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5855. 
     
     
       45. The antibody of  claim 1 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5856. 
     
     
       46. The antibody of  claim 1 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5884. 
     
     
       47. An article of manufacture comprising a container and the antibody of  claim 1 . 
     
     
       48. The article of manufacture of  claim 47  which further comprises a carrier. 
     
     
       49. The article of manufacture of  claim 47  which further comprises a label or package insert. 
     
     
       50. The antibody of  claim 3  which is produced in bacteria. 
     
     
       51. An isolated antibody that inhibits the growth of Ovr110-expressing cancer cells, wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by a hybridoma selected from the group consisting of American Type Culture Collection accession number PTA-5180, PTA-5855, PTA-5856 and PTA-5884. 
     
     
       52. The antibody of  claim 51  which is a monoclonal antibody produced by a hybridoma selected from the group consisting of American Type Culture Collection accession number PTA-5180, PTA-5855, PTA-5856 and PTA-5884. 
     
     
       53. The antibody of  claim 51  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5180. 
     
     
       54. The antibody of  claim 51  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5855. 
     
     
       55. The antibody of  claim 51  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5856. 
     
     
       56. The antibody of  claim 51  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5884. 
     
     
       57. The antibody of  claim 51 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5180. 
     
     
       58. The antibody of  claim 51 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5855. 
     
     
       59. The antibody of  claim 51 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5856. 
     
     
       60. The antibody of  claim 51 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5884. 
     
     
       61. An article of manufacture comprising a container and the antibody of  claim 51 . 
     
     
       62. The article of manufacture of  claim 61  which further comprises a carrier. 
     
     
       63. The article of manufacture of  claim 61  which further comprises a label or package insert. 
     
     
       64. A method of killing an Ovr110-expressing cancer cell, comprising contacting the cancer cell with the antibody of  claim 51 , thereby killing the cancer cell. 
     
     
       65. The method of  claim 64 , wherein the cancer cell is selected from the group consisting of ovarian, pancreatic, lung and breast cancer cell. 
     
     
       66. The method of  claim 64 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
       67. The method of  claim 66 , wherein the cytotoxic agent is a toxin selected from the group consisting of maytansinoid, ricin, saporin and calicheamicin or a radioisotope. 
     
     
       68. The method of  claim 64 , wherein the antibody is administered in conjunction with at least one chemotherapeutic agent. 
     
     
       69. The method of  claim 68  wherein the chemotherapeutic agent is paclitaxel or derivatives thereof. 
     
     
       70. A method for determining if cells in a sample express Ovr110 comprising
 (a) contacting a sample of cells with an Ovr110 antibody of  claim 51  under conditions suitable for specific binding of the Ovr110 antibody to Ovr110, and 
 (b) determining the level of binding of the antibody to cells in the sample, or the level of Ovr110 antibody internalization by cells in said sample, 
 wherein Ovr110 antibody binding to cells in the sample or internalization of the Ovr110 antibody by cells in the sample indicate cells in the sample express Ovr110. 
 
     
     
       71. A method for detecting Ovr110 overexpression in a subject in need thereof comprising,
 (a) combining a serum sample of a subject with an Ovr110 antibody of  claim 51  under conditions suitable for specific binding of the Ovr110 antibody to Ovr110 in said serum sample 
 (b) determining the level of Ovr110 in the serum sample, and 
 (c) comparing the level of Ovr110 determined in step b to the level of Ovr110 in a control, 
 wherein an increase in the level of Ovr110 in the serum sample from the subject as compared to the control is indicative of Ovr110 overexpression in the subject. 
 
     
     
       72. The method of  claim 71  wherein the subject has cancer. 
     
     
       73. The method of  claim 72  wherein the subject has breast or ovarian cancer. 
     
     
       74. The antibody of  claim 28  which is a monoclonal, chimeric, human or humanized antibody. 
     
     
       75. The antibody of  claim 74  which is produced in bacteria. 
     
     
       76. The antibody of  claim 28  which competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5180. 
     
     
       77. The antibody of  claim 28  which competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5855. 
     
     
       78. The antibody of  claim 28  which competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5856. 
     
     
       79. The antibody of  claim 28  which competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5884. 
     
     
       80. The antibody of  claim 28  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5180. 
     
     
       81. The antibody of  claim 28  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5855. 
     
     
       82. The antibody of  claim 28  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5856. 
     
     
       83. The antibody of  claim 28  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5884. 
     
     
       84. An article of manufacture comprising a container and the antibody of  claim 28 . 
     
     
       85. The article of manufacture of  claim 84  which further comprises a carrier. 
     
     
       86. The article of manufacture of  claim 84  which further comprises a label or package insert. 
     
     
       87. A method of killing an Ovr110-expressing cancer cell, comprising contacting the cancer cell with the antibody of  claim 28 , thereby killing the cancer cell. 
     
     
       88. The method of  claim 87 , wherein the cancer cell is selected from the group consisting of ovarian, pancreatic, lung and breast cancer cell. 
     
     
       89. The method of  claim 87 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
       90. The method of  claim 89 , wherein the cytotoxic agent is a toxin selected from the group consisting of maytansinoid, ricin, saporin and calicheamicin or a radioisotope. 
     
     
       91. The method of  claim 87 , wherein the antibody is administered in conjunction with at least one chemotherapeutic agent. 
     
     
       92. The method of  claim 91  wherein the chemotherapeutic agent is paclitaxel or derivatives thereof. 
     
     
       93. A method for determining if cells in a sample express Ovr110 comprising
 (a) contacting a sample of cells with an Ovr110 antibody of  claim 28  under conditions suitable for specific binding of the Ovr110 antibody to Ovr110, and 
 (b) determining the level of binding of the antibody to cells in the sample, or the level of Ovr110 antibody internalization by cells in said sample, 
 wherein Ovr110 antibody binding to cells in the sample or internalization of the Ovr110 antibody by cells in the sample indicate cells in the sample express Ovr110. 
 
     
     
       94. A method for detecting Ovr110 overexpression in a subject in need thereof comprising,
 (a) combining a serum sample of a subject with an Ovr110 antibody of  claim 28  under conditions suitable for specific binding of the Ovr110 antibody to Ovr110 in said serum sample, 
 (b) determining the level of Ovr110 in the serum sample, and 
 (c) comparing the level of Ovr110 determined in step b to the level of Ovr110 in a control, 
 wherein an increase in the level of Ovr110 in the serum sample from the subject as compared to the control is indicative of Ovr110 overexpression in the subject. 
 
     
     
       95. The method of  claim 94  wherein the subject has cancer. 
     
     
       96. The method of  claim 95  wherein the subject has breast or ovarian cancer. 
     
     
       97. An isolated monoclonal antibody produced by a hybridoma selected from the group consisting of American Type Culture Collection accession number PTA-5180, PTA-5855, PTA-5856 and PTA-5884. 
     
     
       98. The antibody of  claim 97  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5180. 
     
     
       99. The antibody of  claim 97  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5855. 
     
     
       100. The antibody of  claim 97  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5856. 
     
     
       101. The antibody of  claim 97  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5884. 
     
     
       102. The antibody of  claim 97  which is a chimeric, human or humanized antibody variant thereof. 
     
     
       103. The antibody of  claim 102  which is produced in bacteria. 
     
     
       104. The antibody of  claim 97  which is conjugated to a growth inhibitory agent or a cytotoxic agent. 
     
     
       105. The antibody of  claim 104  wherein the cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 
     
     
       106. The antibody of  claim 105 , wherein the toxin is selected from the group consisting of ricin, saponin, maytansinoid and calicheamicin. 
     
     
       107. The antibody of  claim 97  which is detectably labeled. 
     
     
       108. The antibody of  claim 107  wherein the label is selected from the group comprising radiolabels, fluorescent labels, gold particles, and enzymatic labels. 
     
     
       109. An isolated cell that produces the antibody of  claim 97 . 
     
     
       110. A composition comprising the antibody of  claim 97  and a carrier. 
     
     
       111. The composition of  claim 110 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
       112. The composition of  claim 110 , wherein the antibody is a chimeric, human or humanized antibody and the carrier is a pharmaceutical carrier. 
     
     
       113. An article of manufacture comprising a container and the antibody of  claim 97 . 
     
     
       114. The article of manufacture of  claim 113  which further comprises a carrier. 
     
     
       115. The article of manufacture of  claim 113  which further comprises a label or package insert. 
     
     
       116. A method of killing an Ovr110-expressing cancer cell, comprising contacting the cancer cell with the antibody of  claim 97 , thereby killing the cancer cell. 
     
     
       117. The method of  claim 116 , wherein the cancer cell is selected from the group consisting of ovarian, pancreatic, lung and breast cancer cell. 
     
     
       118. The method of  claim 116 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
       119. The method of  claim 118 , wherein the cytotoxic agent is a toxin selected from the group consisting of maytansinoid, ricin, saporin and calicheamicin or a radioisotope. 
     
     
       120. The method of  claim 116 , wherein the antibody is administered in conjunction with at least one chemotherapeutic agent. 
     
     
       121. The method of  claim 120  wherein the chemotherapeutic agent is paclitaxel or derivatives thereof. 
     
     
       122. A method for determining if cells in a sample express Ovr110 comprising
 (a) contacting a sample of cells with an Ovr110 antibody of  claim 97  under conditions suitable for specific binding of the Ovr110 antibody to Ovr110, and 
 (b) determining the level of binding of the antibody to cells in the sample, or the level of Ovr110 antibody internalization by cells in said sample, 
 wherein Ovr110 antibody binding to cells in the sample or internalization of the Ovr110 antibody by cells in the sample indicate cells in the sample express Ovr110. 
 
     
     
       123. A method for detecting Ovr110 overexpression in a subject in need thereof comprising,
 (a) combining a serum sample of a subject with an Ovr110 antibody of  claim 97  under conditions suitable for specific binding of the Ovr110 antibody to Ovr110 in said serum sample, 
 (b) determining the level of Ovr110 in the serum sample, and 
 (c) comparing the level of Ovr110 determined in step b to the level of Ovr110 in a control, 
 wherein an increase in the level of Ovr110 in the serum sample from the subject as compared to the control is indicative of Ovr110 overexpression in the subject. 
 
     
     
       124. The method of  claim 123  wherein the subject has cancer. 
     
     
       125. The method of  claim 124  wherein the subject has breast or ovarian cancer. 
     
     
       126. An isolated antibody that internalizes upon binding to Ovr110 on a mammalian cell, wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by a hybridoma selected from the group consisting of American Type Culture Collection accession number PTA-5180, PTA-5855, PTA-5856 and PTA-5884. 
     
     
       127. The antibody of  claim 126  which is a monoclonal antibody produced by a hybridoma selected from the group consisting of American Type Culture Collection accession number PTA-5180, PTA-5855, PTA-5856 and PTA-5884. 
     
     
       128. The antibody of  claim 126  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5180. 
     
     
       129. The antibody of  claim 126  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5855. 
     
     
       130. The antibody of  claim 126  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5856. 
     
     
       131. The antibody of  claim 126  which is a monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5884. 
     
     
       132. The antibody of  claim 126 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5180. 
     
     
       133. The antibody of  claim 126 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5855. 
     
     
       134. The antibody of  claim 126 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5856. 
     
     
       135. The antibody of  claim 126 , wherein the antibody competes for binding to the same epitope as the epitope bound by the monoclonal antibody produced by the hybridoma of American Type Culture Collection accession number PTA-5884. 
     
     
       136. An article of manufacture comprising a container and the antibody of  claim 126 . 
     
     
       137. The article of manufacture of  claim 136  which further comprises a carrier. 
     
     
       138. The article of manufacture of  claim 136  which further comprises a label or package insert. 
     
     
       139. A method of killing an Ovr110-expressing cancer cell, comprising contacting the cancer cell with the antibody of  claim 126 , thereby killing the cancer cell. 
     
     
       140. The method of  claim 139 , wherein the cancer cell is selected from the group consisting of ovarian, pancreatic, lung and breast cancer cell. 
     
     
       141. The method of  claim 139 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
       142. The method of  claim 141 , wherein the cytotoxic agent is a toxin selected from the group consisting of maytansinoid, ricin, saporin and calicheamicin or a radioisotope. 
     
     
       143. The method of  claim 139 , wherein the antibody is administered in conjunction with at least one chemotherapeutic agent. 
     
     
       144. The method of  claim 143  wherein the chemotherapeutic agent is paclitaxel or derivatives thereof. 
     
     
       145. A method for determining if cells in a sample express Ovr110 comprising
 (a) contacting a sample of cells with an Ovr110 antibody of  claim 126  under conditions suitable for specific binding of the Ovr110 antibody to Ovr110, and 
 (b) determining the level of binding of the antibody to cells in the sample, or the level of Ovr110 antibody internalization by cells in said sample, 
 wherein Ovr110 antibody binding to cells in the sample or internalization of the Ovr110 antibody by cells in the sample indicate cells in the sample express Ovr110. 
 
     
     
       146. A method for detecting Ovr110 overexpression in a subject in need thereof comprising,
 (a) combining a serum sample of a subject with an Ovr110 antibody of  claim 126  under conditions suitable for specific binding of the Ovr110 antibody to Ovr110 in said serum sample, 
 (b) determining the level of Ovr110 in the serum sample, and 
 (c) comparing the level of Ovr110 determined in step b to the level of Ovr110 in a control, 
 wherein an increase in the level of Ovr110 in the serum sample from the subject as compared to the control is indicative of Ovr110 overexpression in the subject. 
 
     
     
       147. The method of  claim 146  wherein the subject has cancer. 
     
     
       148. The method of  claim 147  wherein the subject has breast or ovarian cancer.